Diversity of the CD8+ T Cell Repertoire Elicited against an Immunodominant Epitope Does Not Depend on the Context of Infection

Department of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
The Journal of Immunology (Impact Factor: 4.92). 02/2010; 184(6):2958-65. DOI: 10.4049/jimmunol.0903493
Source: PubMed


The diversity of the pathogen-specific T cell repertoire is believed to be important in allowing recognition of different pathogen epitopes and their variants and thereby reducing the opportunities for mutation-driven pathogen escape. However, the extent to which the TCR repertoire can be manipulated by different vaccine strategies so as to obtain broad diversity and optimal protection is incompletely understood. We have investigated the influence of the infectious/inflammatory context on the TCR diversity of the CD8(+) T cell response specific for the immunodominant epitope in C57BL/6 mice, derived from glycoprotein B of HSV-1. To that effect, we compared TCR V segment utilization, CDR3 length, and sequence diversity of the response to natural HSV-1 infection with those elicited by either Listeria monocytogenes or vaccinia virus expressing the immunodominant epitope in C57BL/6 mice. We demonstrate that although the type of infection in which the epitope was encountered can influence the magnitude of the CD8(+) T cell responses, TCR beta-chain repertoires did not significantly differ among the three infections. These results suggest that widely different live vaccine vectors may have little impact upon the diversity of the induced CTL response, which has important implications for the design of live CTL vaccine strategies against acute and chronic infections.

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Available from: Megan J Smithey, Jul 21, 2014
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    • "Peptides were synthesized by the solid-phase method, and purified by HPLC to >98% purity (UF Peptides, Ferrara, Italy). HSV1 Kb-restricted peptides SSIEFARL (SSI), derived from glycoprotein B (gB) [57], [58]; ITAYGLVL (ITA), derived from glycoprotein K (gK) [59], [60]; and QTFDFGRL (QTF), derived from ribonucleotide reductase 1 (RR1) [61], were used to evaluate anti-HSV1 T-cell responses in C57BL/6 mice. HSV1 Kd-restricted peptide DYATLGVGV (DYA), derived from ICP27 [62], [63], and SLKMADPNRFRGKDLP (SLK), which includes both the Hb-restricted CD4 and Kd-restricted CD8 immunodominant epitopes derived from glycoprotein D (gD) [64]–[66], were used to evaluate anti-HSV1 T-cell responses in BALB/c mice. "
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